The behavioral pharmacological profile of a drug in a pertinent species is necessary for evaluating quantitatively how the drug functions as a reinforcer and how use or abuse of the drug effects other aspects of the subject's behavior. Ongoing studies on the direct behavioral effects of drugs include a number of different paradigms. A variety of studies involve observations of changes in spontaneous and learned behavior following acute or chronic injections of drugs. For example, we have recently shown that plasma butyrylcholinesterase (BChE ), when added to the blood of squirrel monkeys, speeds the metabolism of cocaine. We have also shown that squirrel and rhesus monkeys differs in the amount of BChE naturally occurring in plasma and these differences result in differing rates of cocaine metabolism. Preliminary work with locomotor activity in rats supports the conclusion that alterations in metabolism might reduce the acute effects of cocaine by speeding its metabolism. Animals repeatedly injected with cocaine in the presence of a novel stimulus show an increased locomotor response to that stimulus. Recent studies have shown that such stimuli can also serve as conditioned reinforcers, and thus might further facilitate drug-taking behavior. The effects of chronic nicotine exposure have been investigated on both schedule- controlled behavior and spontaneous locomotor activity. Chronic exposure was not associated with tolerance, nor was there an obvious withdrawal syndrome observed. A wide range of studies are ongoing to investigate pharmacological mechanisms that determine how psychoactive drugs such as nicotine, methamphetamine, and cocaine function as discriminative stimuli. Rats trained to discriminate a mixture of phentermine and fenfluamine from saline show a generalization profile which suggests that this drug mixture does not result in a unique drug cue. In animals trained to discriminate nicotine from saline, chronic caffeine exposure does not disrupt the ability to discriminate the nicotine cue. However, amphetamine does generalize to nicotine in control animals, but does not in animals chronically administered caffeine, suggesting a unique interaction between these two psychomotor stimulants. In monkeys chronically treated with caffeine there is a marked enhancement of the stimulant effects of nicotine but not of amphetamine on operant behavior.